The purpose of this application is to permit continuing support for the multidisciplinary investigative program in cardiovascular research at the Massachusetts General Hospital which aims to increase the basic understanding of cardiovascular function and to apply this knowledge to improving the prevention and management of cardiovascular disease. This program involves the joint investigative talents and physical facilities of several important laboratories of the Departments of Medicine and Physiology: the Cardiac and Cardiorenal Research Laboratories of Massachusetts General Hospital and the Microprobe Analysis Laboratory of Harvard Medical School. This application brings together investigators studying the effects of circulatory insufficiency on the heart, and kidneys. In both tissues cell swelling is a regular, but preventable consequence of ischemia. We have found in heart and kidney in vivo that prevention of swelling during ischemia can protect function and decrease subsequent tissue necrosis. This observation has been confirmed in vitro with cultured renal tubule cells. We propose to determine the mechanism realting cell swelling during anoxia or ischemia to cell death. A newly described natriuretic factor extractable from the hypothalamus will be investigated in animals to delineate its physiologic functions in the regulation of body sodium content and extracellular fluid volume. Other basic studies in renal function and ion transport will be pursued that are necessary to provide understanding of body fluid regulation.